Targeting GLP-1 receptors for repeated magnetic resonance imaging differentiates graded losses of pancreatic beta cells in mice

• Published in: Diabetologia Vol. 58; no. 2; pp. 304 - 312
• Main Authors: Vinet, Laurent, Lamprianou, Smaragda, Babič, Andrej, Lange, Norbert, Thorel, Fabrizio, Herrera, Pedro Luis, Montet, Xavier, Meda, Paolo
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2015; Springer Nature B.V
• Subjects: Animals; Diabetes; Female; Glucagon; Glucagon - metabolism; Human Physiology; Insulin; Insulin-Secreting Cells - metabolism; Internal Medicine; Longitudinal studies; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Methods; Mice; Mice, Transgenic; Microscopy, Fluorescence; Molecular Probes; Nanoparticles; Peptide Fragments - metabolism; Peptides; Physiology; Radiation; Receptors, Glucagon - metabolism; Tissue Distribution; Tomography; United States > US; Switzerland; Europe; Targeted iron oxide nanoparticles; Multimodality probe; Exendin; Magnetic resonance imaging; Glucagon-like peptide 1 receptors; Beta cell mass
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-014-3442-2

Aims/hypothesis Non-invasive imaging of beta cells is a much-needed development but is one that faces significant biological and technological hurdles. A relevant imaging method should at least allow for an evaluation over time of the mass of beta cells under physiological and pathological conditions, and for an assessment of novel therapies. We, therefore, investigated the ability of a new MRI probe to repeatedly measure the loss of beta cells in a rodent model. Methods We developed an innovative nanoparticle probe that targets the glucagon-like peptide 1 receptor, and can be used for both fluorescence imaging and MRI. Using fluorescence, we characterised the specificity and biodistribution of the probe. Using 1.5T MRI, we longitudinally imaged the changes in insulin content in male and female mice of the RIP-DTr strain, which mimic the changes expected in type 1 and type 2 diabetes, respectively. Results We showed that this probe selectively labelled beta cells in situ, imaged in vivo native pancreatic islets and evaluated their loss after diphtheria toxin administration, in a model of graded beta cell deletion. Thus, using clinical MRI, the probe quantitatively differentiates, in the same mouse strain, between female animals featuring a 50% loss of beta cells and the males featuring an almost complete loss of beta cells. Conclusions/interpretation The approach addresses several of the hurdles that have so far limited the non-invasive imaging of beta cells, including the potential to repeatedly monitor the very same animals using clinically available equipment, and to differentiate graded losses of beta cells.